The major component of morbidity and mortality attributable to cardiovascular disease occurs as a consequence of the partial or complete blockage of vessels carrying blood in the coronary vascular system and in peripheral vasculature. When such vessels are occluded, various clinical syndromes may result from death of tissue previously nourished by the occluded vessels or inability of the vessels to transport sufficient blood supply to regions requiring high blood consumption and accompanying nutrients. In some individuals, blood vessel occlusion is partially compensated by the natural process of angiogenesis, in which new conduits are formed to replace the function of the impaired vessels. These new conduits, called "collateral" vessels, may facilitate restoration of blood flow to the deprived tissue, thereby constituting "natural bypasses" around the occluded vessels. However, some individuals are unable to generate sufficient collateral vessels to manage the consequences of diminished blood flow from cardiovascular disease.
At present, blood vessel occlusions are usually treated by mechanically enhancing blood flow or by medical reduction of oxygen demands in the involved tissues or organs. Mechanical enhancements are provided most commonly by (1) employing surgical techniques that attach autologous or synthetic vascular conduits proximal and distal to the areas of occlusion, thereby providing bypass grafts, or (2) revascularization by various means to physically enlarge the vascular lumen at the site of occlusion. These procedures involve such devices as balloons, endovascular knives (atherectomy), endovascular drills, and the like. The surgical approach is accompanied by significant morbidity and even mortality, while the angioplasty-type processes are complicated by recurrent stenoses in 25-35% of cases. Successful mechanical revascularization depends, inter alia, on accessibility of the occluding stenosis to such procedures. Clearly, there remains a pressing need for means to stimulate angiogenesis to provide collateral blood flow by non-invasive or minimally invasive procedures.